"Old School" Islet Purification Based on the Unit Gravity Sedimentation as a Rescue Technique for Intraportal Islet Transplantation-A Case Report.

Here, we present a case that required a supplemental "old school" islet purification for a safe intraportal infusion. Following pancreas procurement from a brain-dead 26-year-old male donor (body mass index: 21.9), 24.6 ml of islet tissue was isolated after continuous density gradient centrifugation. The islet yield was 504,000 islet equivalent (IEQ), distributed among the following three fractions: 64,161 IEQ in 0.6 ml of pellet, 182,058 IEQ in 10 ml, and 258,010 IEQ in 14 ml with 95%, 20%, and 10% purity, respectively. After a 23-h culture, we applied supplemental islet purification, based on the separation of tissue subfractions during unit gravity sedimentation, a technique developed over 60 years ago ("old school"). This method enabled the reduction of the total pellet volume to 11.6 ml, while retaining 374,940 IEQ with a viability of over 90%. The final islet product was prepared in three infusion bags, containing 130,926 IEQ in 2.6 ml of pellet, 108,079 IEQ in 4 ml of pellet, and 135,935 IEQ in 5 ml of pellet with 65%, 40%, and 30% purity, respectively, and with the addition of unfractionated heparin (70 units/kg body weight). Upon the islet infusion from all three bags, portal pressure increased from 7 to 16 mmHg. Antithrombotic prophylaxis with heparin was continued for 48 h after the infusion, with target activated partial thromboplastin time 50-60 s, followed by fractionated heparin subcutaneous injections for 2 weeks. ß-Cell graft function assessed on day 75 post-transplantation was good, according to Igls criteria, with complete elimination of severe hypoglycemic episodes and 50% reduction in insulin requirements. Time spent within the target glucose range (70-180 mg/dl) improved from 42% to 98% and HbA1c declined from 8.7% to 6.7%. Supplemental "old school" islet purification allowed for the safe and successful utilization of a robust and high-quality islet preparation, which otherwise would have been discarded.

Patients seeking information about colonoscopy - lessons learned from Google.

INTRODUCTION: Every year in the USA over 14 million colonoscopies are performed. It requires high-quality examinations as well as a relevant information strategy. Colonoscopy compliance is not satisfactory, which to some extent might be related to patients' attitudes towards colonoscopy, which are based on information and emotions. AIM: In the current study we addressed the questions of what kind of information people seek and get when they search the Internet for "colonoscopy". MATERIAL AND METHODS: Using the Google Trends web facility we analysed search results of "colonoscopy", related searches, and annual and weekly search trends. Fields of interest analysis was performed based on the related searches. RESULTS: Patients are generally offered quality data on the first result page of a Google search biased only by Wikipedia scoring first on the result list. The number of "colonoscopy" searches is stable over the week with a significant decrease on weekends, and stable over the year with significant decrease around Thanksgiving day and in the Christmas/New Year's Eve Period. The most common field of search is colonoscopy preparation, thus underlining the importance of this part of colonoscopy. CONCLUSIONS: Internet search provides abundant information on colonoscopy. In general, this information is accessible, preferred by patients, and of good quality. This should be kept in mind by healthcare providers while educating patients about colonoscopy.

Expression of HTRA Genes and Its Association with Microsatellite Instability and Survival of Patients with Colorectal Cancer.

HtrA proteases regulate cellular homeostasis and cell death. Their dysfunctions have been correlated with oncogenesis and response to therapeutic treatment. We investigated the relation between HtrA1-3 expression and clinicopathological, and survival data, as well as the microsatellite status of tumors. Sixty-five colorectal cancer patients were included in the study. The expression of HTRA1-3 was estimated at the mRNA and protein levels by quantitative PCR and immunoblotting. Microsatellite status was determined by high-resolution-melting PCR. We found that the HTRA1 mRNA level was higher in colorectal cancer tissue as compared to the unchanged mucosa, specifically in primary lesions of metastasizing cancer. The levels of HtrA1 and HtrA2 proteins were reduced in tumor tissue when compared to unchanged mucosa, specifically in primary lesions of metastasizing disease. Moreover, a decrease in HTRA1 and HTRA2 transcripts' levels in cancers with a high level of microsatellite instability compared to microsatellite stable ones has been observed. A low level of HtrA1 or/and HtrA2 in cancer tissue correlated with poorer patient survival. The expression of HTRA1 and HTRA2 changes during colorectal carcinogenesis and microsatellite instability may be, at least partially, associated with these changes. The alterations in the HTRA1/2 genes' expression are connected with metastatic potential of colorectal cancer and may affect patient survival.

Ophthalmologic Diseases in Kidney Transplant Recipients: A Single-Center Prospective Study.

BACKGROUND: Kidney transplant (KTx) recipients usually experience many comorbidities (eg, hypertension, diabetes, cardiovascular disease, glaucoma). They usually are older and have some ophthalmologic disorders, which may deteriorate after Ktx and some others may develop. OBJECTIVE: We aimed to review a 1-year examination of the eyesight characteristics in patients after KTx. METHODS: The study encompassed 82 eyes in 41 patients who underwent KTx in the years 2014 to 2018. All patients had visual acuity measurement, tonometry, slit lamp examination, and spectroscopic optical coherence tomography. RESULTS: The most frequently observed changes during the 1-year observation were cataract (46%), hypertensive angiopathy (20%), and glaucoma (20%). One year after the renal transplant visual acuity declined in 22 patients (54%). In 45% of those with eyesight deterioration the cause was cataract, while in patients with no changes in eyesight (n = 9) cataract was not diagnosed. Patients with cataracts had been more often treated with high doses of steroids (steroid boluses), mainly because of acute rejection, which was significantly associated with cataract developing after Ktx (42% vs 11%; P = .019). On univariate analysis Charlson Comorbidity Index, total ischemic time, and steroid boluses were significantly associated with cataract developing after Ktx; none of these factors were an independent predictor on multivariate analysis. CONCLUSIONS: The most common ophthalmologic diagnoses in patients after Ktx include cataract, glaucoma, and hypertensive angiopathy. Visual acuity deterioration, seen so often in the studied group of the patients, was mainly the effect of cataract progress. The effect of steroid boluses on cataract progress was meaningful.

Pregnancy After Kidney Transplantation With Maternal and Pediatric Outcomes: A Single-Center Experience.

Outcomes of pregnancies after kidney transplantation were evaluated. Thirty-one pregnancies in 26 women were noted. The mean maternal age at pregnancy was 31 ± 5 years (range, 23-44 years). The interval between transplantation and conception was 54 ± 51 months (range, 7-213 months). The mean serum creatinine concentration before conception was 1.28 ± 0.4 mg/dL (range, 0.8-2.45 mg/dL), and mean estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration) was 62 ± 18 mL/min/1.73 m2 (range, 27-106 mL/min/1.73 m2). There were no maternal deaths. There was 1 case of suspected acute rejection after delivery. There was 1 case of graft loss during pregnancy. Maternal complications included edema (6/26), hypertension (7/26), increase of (2/26) or appearance of proteinuria (5/26), and preeclampsia (4/26). Mean creatinine increase during pregnancy was 0.02 mg/dL. Mean creatinine 1 year after pregnancy was 1.54 mg/dL (±0.8 mg/dL). There were 19 cesarean sections. Fetal outcomes included 25 live births, 4 abortions, and 2 stillbirths. Out of 25 live births, 22 children were considered healthy, 2 children had congenital defects, and there were 2 deaths at neonatal age. Mean pregnancy age was 35 ± 4 weeks (range, 24-40 weeks). The rate of premature deliveries was 15 of 25. Mean neonate birth weight was 2363 ± 1029 grams (range, 490-4100 grams). The rate of babies small for gestational age was 19%. During follow-up (range, 0.5-30 years) 5 of 26 patients lost grafts (between 3 and 15 years after pregnancy); most (20) of the children previously considered healthy had good long-term development. Our results confirm that risk of pregnancy in kidney transplant recipients can be accepted, and children considered healthy at delivery develop well.

Diagnostic and therapeutic recommendations in pancreatic ductal adenocarcinoma. Recommendations of the Working Group of the Polish Pancreatic Club.

These recommendations refer to the current management in pancreatic ductal adenocarcinoma (PDAC), a neoplasia characterised by an aggressive course and extremely poor prognosis. The recommendations regard diagnosis, surgical, adjuvant and palliative treatment, with consideration given to endoscopic and surgical methods. A vast majority of the statements are based on data obtained in clinical studies and experts' recommendations on PDAC management, including the following guidelines: International Association of Pancreatology/European Pancreatic Club (IAP/EPC), American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN) and Polish Society of Gastroenterology (PSG) and The National Institute for Health and Care Excellence (NICE). All recommendations were voted on by members of the Working Group of the Polish Pancreatic Club. Results of the voting and brief comments are provided with each recommendation.

Metformin and Colorectal Cancer - A Systematic Review.

OBJECTIVES: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths. The development of preventive strategies in CRC has been the subject of much research. Multiple studies have shown an association between diabetes and CRC. In addition to its glucose-lowering properties, metformin might have an additional role in the prevention and treatment of CRC. OUR OBJECTIVE: was to summarize findings on role of metformin in colorectal cancer. METHODS: We conducted a systematic review of the PubMed and Cochrane databases from January 2005 to December 2017 in search for studies on the association between metformin and CRC. RESULTS: Of the total of 189 studies identified by the search, we excluded 123 studies and reviewed the remaining 66 studies on cell lines, animals, patients with diabetes, and healthy subjects. In vitro and animal studies have shown a protective effect of metformin use on the incidence of CRC and amplification of the therapeutic effects of CRC chemotherapy. Studies on patients with type 2 diabetes treated with metformin analyzed data on total of 146 496 patients. The results of those studies on the role of metformin in CRC suggest risk reduction and potential applications within therapeutic regimens, although some of those are conflicting. CONCLUSION: Further studies are warranted to define the role of metformin in both prevention and treatment of CRC.

Colonoscopy as Part of Pre-Transplant Work-Up in Successful Kidney Transplant Candidates: Single-Center Experience and Review of Literature.

BACKGROUND Screening colonoscopy is not obligatory in kidney pre-transplant work-up guidelines. According to recommendations, only transplant recipients over age 50 years should be screened. The aim of this study was to characterize endoscopic findings revealed as part of pre-transplant work-up. MATERIAL AND METHODS We retrospectively reviewed pre-transplant work-up charts of 434 adult patients who received a cadaveric donor kidney transplantation (KT) from 2012 to 2015. Endoscopic findings analysis with age subgroup (<50 and ³50) analysis were performed. RESULTS Out of 434 of patients that underwent KT, 29% have had a colonoscopy. In 75.6% of those, pathologies were found. Hemorrhoids were found in 33% and polyps in 30.7% of patients. Adenoma detection rate (ADR) was 18.1% (67.5% distal predominance). Advanced ADR was 10.2% (distal predominance). Diverticulosis was found in 28.3% of patients and ulcerative colitis was found in 2.4%. In age subgroup analysis, ADR was higher in patients ³50 years compared to those <50 years (21.6% vs. 4%; p=0.041). CONCLUSIONS Colonoscopy as part of pre-transplant work-up enables removal of precancerous lesions and management of benign findings. All candidates meeting criteria for the general population should be screened. Patients under age 50 years could also benefit from colonoscopy as part of the pre-transplant work-up. Therefore, we suggest that baseline colonoscopy should be included in pre-transplant work-up guidelines for all patients, regardless of age. However, further studies are needed to confirm this recommendation.

Gallbladder Pathologies in Kidney Transplant Recipients: Single-Center Experience and a Review of the Literature.

BACKGROUND In patients with end-stage renal disease, cholelithiasis is observed with an increased frequency. In transplant recipients, symptoms might be obscured, which may delay the diagnosis and lead to complications. The aim of our study was to evaluate the frequency of gallbladder pathologies in kidney transplant recipients (KTRs) in the Caucasian population, and to discuss the potential benefits of prophylactic cholecystectomy before kidney transplantation (KT). MATERIAL AND METHODS Data from 434 patients who underwent KT was analyzed. Demographic data along with gallbladder status were collected from the pre-transplantation charts. We compared our results to data from the general Polish population. RESULTS In our analyzed group of KTRs, there were 284 men and 150 women. Complete data, including abdominal ultrasound description, were available in 412 cases. In this group, 36 patients (8.74%) underwent cholecystectomy before KT. Other gallbladder pathologies (gallstones and polyps) were found in 41 patients (9.95%) at pre-transplantation evaluation. The incidence of gallbladder pathologies in KTRs, being mostly cholelithiasis, was higher than in the general Polish population. CONCLUSIONS In specific age subgroups of KTRs, the frequency of gallbladder pathologies was higher than in the general population. Prophylactic cholecystectomy may potentially offer benefits in these subgroups of patients.

Cancer stem cells as targets for DC-based immunotherapy of colorectal cancer.

The therapy of colorectal cancer (CRC) patients is often unsuccessful because of the presence of cancer stem cells (CSCs) resistant to conventional approaches. Dendritic cells (DC)-based protocols are believed to effectively supplement CRC therapy. Our study was aimed to assess how the number and properties of CSCs isolated from tumor tissue of CRC patients will affect the biological characteristics of in vitro modified DCs. Similar procedures were conducted with the using of CRC HCT116 and HT29 cell lines. We found that the detailed configuration of CSC-like markers significantly influenced the maturation and activation of DCs after stimulation with cancer cells lysates or culture supernatants. This basic stimulatory effect was enhanced by LPS that is normally present in CRC CSCs niche. The increased number of CD29+ and CD44+ CSCs presented the opposite impact on treated DCs as showed by many significant correlations. The CD133+ CSCs seemed to impair the functions of DCs. The more CD133+ CSCs in tumor sample the lower number of activated DCs evidenced after stimulation. Moreover, our results showed superiority of the spherical culture model over the adherent one since spherical HCT116 and HT29 cells presented similar influence on DCs properties as CRC patients cancer cells. We concluded that the DCs features may depend directly on the properties of CSCs affected by progression status of tumor.

Structured box training improves stability of retraction while multitasking in colorectal surgery simulation.

BACKGROUND: Laparoscopic colorectal surgery has an established role. The ability to multitask (use a retraction tool with one hand and navigate a laparoscopic camera with the other) is desired for efficient laparoscopic surgery. Surgical trainees must learn this skill to perform advanced laparoscopic tasks. The aim was to determine whether a box-training protocol improves the stability of retraction while multitasking in colorectal surgery simulation. MATERIALS AND METHODS: Fifty-eight medical students were recruited to attend a basic laparoscopic box-training course. Ability to perform steady retraction with and without multitasking was measured initially and at the conclusion of the course. RESULTS: Before training, students demonstrated a decrease in performance while multitasking with a greater maximal exerted force, a greater range of force, and a greater standard deviation for traction and minimal exerted force, range of force and a greater standard deviation for countertraction. Statistically significant improvement (lower maximal exerted force and lower range of force) was observed for traction while multitasking after training. After the training, no statistically significant differences were found when the student performed a single task versus multitasking, both for traction and countertraction. CONCLUSIONS: A structured box-training curriculum improved the stability of retraction while multitasking in this colorectal surgery simulation. Although it did not improve stability of retraction as a single task, it did improve stability of retraction while multitasking. After training, this enables the trainee to retract as efficiently while operating the camera as they retract when only focusing on retraction as a single task.

Cost-effectiveness of benign Wirsung duct strictures treatment in chronic pancreatitis.

INTRODUCTION: Chronic pancreatitis (CP) is an important problem for modern medicine, the healthcare system (Poland - NFZ) and the national insurance system (Poland - ZUS). The chronic nature of the disease, the lack of targeted treatment and the low mortality rate lead to an accumulation of patients who demand expensive treatment, both conservative and invasive. Rising costs in health care are forcing the need for a more cost-effective method of treatment. AIM: The primary aim of this study was to perform a retrospective calculation of costs in both surgical and endoscopic treatment, hospital stay, healthcare, and public insurance of patients suffering from chronic pancreatitis. Parallel quality of life analysis was performed. It was possible to develop a cost-effective therapeutic algorithm for patients with an uncomplicated stricture of Wirsung's duct within the Polish health care system. RESULTS: In Poland, the hospital costs of endoscopic treatment of patients with chronic pancreatitis were higher than those of the surgical treatment group despite both resulting in a similar life quality. CONCLUSIONS: From a cost-effectiveness perspective, it was shown that surgical intervention is a more cost-effective therapy than endotherapy. Furthermore, patients with benign stricture of the main pancreatic duct in chronic pancreatitis should not be treated with endotherapy for longer than 12 months.

Surgical decompression of Wirsung duct reduces serum concentration of SPINK1 in patients with chronic pancreatitis.

OBJECTIVES: The primary aim of this study was to determine the blood levels of SPINK1 in patients with chronic pancreatitis (CP) submitted to surgical or endoscopic decompression of pancreatic duct (PD). Additionally, we measured trypsin activity levels. METHODS: Two groups were identified, surgical (group A) and endoscopic (group B). Levels of SPINK1 and trypsin activity were measured at baseline and 6 months after pancreatic duct decompression and then compared within the groups. SPINK1 levels were determined with Human ELISA Kit. RESULTS: Group A and B were made up of 30 and 28 patients, respectively. Baseline features of the groups were similar. A decrease in SPINK1 levels was significant only in group A 46.88 to 16.10 ng/mL (p = 0.001). On the contrary, trypsin activity changed significantly in group B 40.01 to 34.92 mU/mL (p = 0.01). Patients of group A showed a significant increase in BMI, before and after treatment. The pain score pre- and post-treatment reduced significantly in both groups (p < 0.001). CONCLUSIONS: We demonstrate for the first time a significant decrease of SPINK1 levels after surgical decompression of PD and a reduction of trypsin activity analysis after endoscopic decompression. The meaning of this phenomena is yet to be explained and it should be further explored.

FasR and FasL in colorectal cancer.

Colorectal cancer (CRC) is one of the most common solid organ cancers prevalent worldwide causing, in spite of advancing therapeutic methodology, high rate of patient mortality, especially due to metastasis development. The cancer stem cell (CSC) theory of tumor growth indicates that CSCs within the tumor mass have great capacity to initiate and sustain tumor growth. Following the suggestion that Fas signaling can be engaged in apoptosis, tumor maintenance, senescence or DICE (death induced by CD95 or CD95L elimination), the attempts to broaden the knowledge concerning the relationships between CSCs features and FasR/FasL appeared to be necessary. The most important advantage of our study was the simultaneously analysis of CSCs from commonly used CRC lines (HCT116 and HT29) and tumor fragments collected from CRC patients. Moreover, the sphere-promoting expansion of CRC lines brought a specific three-dimensional specific environment for CSC exploration. We further investigated the function of Fas signaling in CRC lines depending on the culture mode as we incubated HCT116 and HT29 cells with anti-FasR agonistic antibodies. It appeared to act in a line-dependent and culture mode-dependent manner and influenced some particular features of CSCs such as spherogenicity, proliferation and phenotype. Additionally, the analysis of mRNA level showed that disease progression is associated with significantly increased expression of FasR and/or FasL. In conclusion, our observation seems to confirm that spherical model of cancer lines is more reliable for some sophisticated analysis because of their greater resemblance to the CSCs from human CRC samples in comparison to commonly used adherent cells, at least according to aspects of their biology analyzed in this study. That can be extended to the resemblance of in vitro sphere forming conditions to the in vivo environment. However, the greatest difference concerns the level of apoptosis, thus, this issue require further experiments.

Dynamics of quality of life improvement after floppy Nissen fundoplication for gastroesophageal reflux disease.

INTRODUCTION: Gastroesophageal reflux disease (GERD) has a negative impact on global quality of life (QOL) of patients. In patients affected by GERD, laparoscopic Nissen fundoplication is one of the most commonly performed laparoscopic procedures worldwide. AIM: To prospectively analyze the dynamics of QOL as well as severity of pain in patients with GERD, before and after laparoscopic floppy Nissen fundoplication. MATERIAL AND METHODS: The study involved 104 consecutive patients operated on for GERD in whom laparoscopic floppy Nissen fundoplication was performed. QOL was assessed before surgery and 1, 3, 6, 12 and 24 months after. The following instruments were used: FACIT-G, FACIT-TS-G, GIQLI, GERD symptom scale. RESULTS: It was found that symptom relief and quality of life improvement presented different dynamics in the postoperative course. Observations revealed relief of symptoms 1 month after surgery and improvement in QOL related to the gastrointestinal tract and pain 3 months after surgery. Global QOL increased significantly as late as 12 months after surgery. CONCLUSIONS: Gastroesophageal reflux disease is a chronic disease of long duration, leading to impairment of quality of life. Patients, apart from typical symptoms of GERD, suffer from pain of significant severity. QOL improves significantly after surgery. Surgical treatment results in relief of GERD symptoms, which leads to gradual improvement of QOL.